Abnormal function of the prefrontal cortex and the amygdala, which interact with each other to control emotions, memory, and decision making, have been implicated in behavioral traits of major mental disorders. Yet, very little is known about how synaptic transmission between the two structures is altered by environmental factors that lead to mental disease. Psychological trauma is one of such factors. It increases risk of developing stronger fear memories in the future, upon exposure to another traumatic event. Here, we will test a hypothesis that a purely psychological trauma makes synaptic connections between prefrontal cortex and amygdala more prone to facilitation during fear learning and that silent synapses, which are generated after psychological trauma, are responsible for the enhanced facilitation. Our preliminary experiments, in which mice are exposed to a conspecific under distress, revealed that such exposure enhances future formation of fear memory in the passive avoidance paradigm. We also found increased number of silent synapses in dmPFC-BLA pathway, which have NMDA receptor, but do not have functional AMPA receptor. Interestingly, the emergence of silence synapses and enhanced avoidance learning were abolished when mice were treated with sub-anesthetic doze of ketamine immediately after psychological trauma. The objectives of the proposal are to understand the process leading to formation of silent synapses, their removal by ketamine and the role silent synapses may play in plastic changes that occur in dmPFC-BLA connections during avoidance learning. The proposal employs optogenetic stimulation of specific axonal fibers and recording of synaptic responses in amygdala slices prepared from animals exposed to combinations of psychological trauma and avoidance learning paradigms. As a parallel approach, we will use immuno-electron microscopy quantification of glutamate receptors in dmPFC-BLA synapses, identified using anterograde tracing. The following questions will be addressed. Are silent synapses between dmPFC and BLA generated by insertion of NMDAR into cell membrane, or by removal of AMPAR? Do they enhance long-term potentiation in dmPFC-BLA pathway in slice? Are they used during passive avoidance learning? What is the mechanism of their elimination by ketamine? By focusing on dmPFC-BLA connection and BLA microcircuit, this study will help elucidate role of defined cellular and synaptic elements underlying emotional traumatization and validate them as a potential target for novel therapies PTSD, depression and related emotional disorders.